Project Summary The positive effects of environmental enrichment and their neural bases have been extensively studied in the rodent. For example, simply modifying an animal?s living environment to promote sensory stimulation can lead to enhancements in hippocampal cognition and neuroplasticity as well as to improve memory deficits associated with neurodegenerative diseases such as Alzheimer?s Disease and aging. While many studies of human aging have focused on individuals aged 65 and older, there are many aspects of cognition (including memory), which show a decline across the lifespan. In addition, current strategies for combating Alzheimer?s Disease are focused heavily on early prevention. Thus, the age group of 40-49 years old represents an understudied age group, which may benefit from a cognitive intervention aimed at improving memory performance. In this proposal, we hypothesize that the exploration of the vast and visually stimulating virtual environments within video games, is a human correlate of environmental enrichment. Although humans, in many ways, already live in an enriched environment, we are constantly adapting to new experiences and situations within our own environment on a daily basis. Video game training may provide a conduit for optimizing the cognitive and neural benefits of environmental enrichment for use as a behavioral intervention for improving memory performance, and possibly, hippocampal function. Recent published data from our lab has already provided evidence that memory performance on unrelated hippocampal-dependent tasks is improved following a 2-week training period on a 3D video game in young adults. In contrast, training on a 2D video game did not result in a boost in memory performance. Here, we seek to explore the neural contributions to this training by evaluating hippocampal structure and function in a pre/post design in adults, aged 40-49 years old. Further, we seek to determine the key features of such an intervention paradigm to explore the key features of video games (the spatial aspect, the complexity of the game, or some combination) to evaluate the potential benefit of environmental enrichment training. These data provide a bridge to much of the rodent literature exploring the benefits of environmental enrichment, extending these principles into humans. Most of the cognitive intervention paradigms currently studied or in use provide a benefit for the precise skill being trained (e.g. improved reaction time over the course of many trials), but they do not generalize to other tasks or cognitive domains. Our preliminary data suggests that following 3D video game training, performance on unrelated, hippocampal-dependent tasks is improved, which is extremely rare and offers great potential as a rehabilitation technique. By focusing on an age group that is fluent with technology, but beginning to exhibit subtle signs of age-related cognitive decline, we can explore the neural and cognitive benefits of such training. The benefits of such training have the potential to be applied to rehabilitation following brain injury and neurological disease, education, and possibly even the benefit of the general population.